Bovine hemesvirus 1 UL49.5 protein inhibits the transporter associated with antigen processing despite complex formation with glycoprotein M
Bovine hemesvirus 1 UL49.5 protein inhibits the transporter associated with antigen processing despite complex formation with glycoprotein M
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DOI：
10.1128/jvi.02707-05
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发表时间：
2006-06-01
影响因子：
5.4
通讯作者：
Wiertz, Emmanuel J. H. J.
中科院分区：
文献类型：
--
作者：
Lipinska, Andrea D.;Koppers-Lalic, Danijela;Wiertz, Emmanuel J. H. J.
牛疱疹病毒1型(BHV-1)通过与抗原处理相关的转运蛋白(TAP)干扰多肽的转运。最近，BHV-1的UL49.5基因产物被鉴定为与观察到的TAP抑制有关的蛋白质。在BHV-1感染的细胞和病毒粒子中，UL49.5蛋白与糖蛋白M(GM)形成复合体。因此，研究了UL49.5是否能结合GM和TAP复合体的相互作用。在同时表达UL49.5和GM的细胞系中，UL49.5似乎是GM功能处理所必需的。免疫荧光共聚焦激光扫描显微镜显示，这两种蛋白质从内质网到跨高尔基体网络的重新分布是相互依赖的。值得注意的是，克隆GM的表达导致了UL49.5对TAP的抑制作用的消除，并阻止了转运蛋白的降解。然而，在BHV-1感染的细胞中，UL49.5和GM表达动力学的差异被认为在感染的早期阶段创造了一个机会之窗，在此期间，UL49.5蛋白可以在没有GM干扰的情况下作用于TAP。此外，在后期，除了UL49.5/GM复合体之外，还可以检测到非GM相关的UL49.5。因此，推测在BHV-1感染过程中，UL49.5的不同功能可以结合在一起，即编辑GM加工和抑制TAP。
Bovine herpesvirus 1 (BHV-1) interferes with peptide translocation by the transporter associated with antigen processing (TAP). Recently, the UL49.5 gene product of BHV-1 was identified as the protein responsible for the observed inhibition of TAP. In BHV-1-infected cells and virions, the UL49.5 protein forms a complex with glycoprotein M (gM). Hence, it was investigated whether UL49.5 can combine the interactions with gM and the TAP complex. In cell lines constitutively expressing both UL49.5 and gM, UL49.5 appears to be required for functional processing of gM. Immunofluorescence-confocal laser scanning microscopy demonstrated that both proteins are interdependent for their redistribution from the endoplasmic reticulum to the trans-Golgi network. Remarkably, expression of cloned gM results in the abrogation of the UL49.5-mediated inhibition of TAP and prevents the degradation of the transporter. However, in BHV-1-infected cells, differences in UL49.5 and gM expression kinetics were seen to create a window of opportunity at the early stages of infection, during which time the UL49.5 protein can act on TAP without gM interference. Moreover, in later periods, non-gM-associated UL49.5 can be detected in addition to the UL49.5/gM complex. Thus, it has been deduced that different functions of UL49.5, editing of gM processing and inhibition of TAP, can be combined during BHV-1 infection.